Field of the Invention
The present disclosure relates to novel polymorphic and co-crystal forms of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one, methods for their preparation, and methods for their use.
Description of Related Technology
The hepatocyte growth factor receptor (“c-Met”) is a unique receptor tyrosine kinase shown to be overexpressed in a variety of malignancies. The ligand for c-Met is hepatocyte growth factor (also known as scatter factor, HGF and SF). Various biological activities have been described for HGF through interaction with c-Met (Hepatocyte Growth Factor-Scatter Factor (HGF-SF) and the c-Met Receptor, Goldberg and Rosen, eds., Birkhauser Verlag-Basel, 67-79 (1993). HGF and c-Met are expressed at abnormally high levels in a large variety of solid tumors. High levels of HGF and/or c-Met have been observed in liver, breast, pancreas, lung, kidney, bladder, ovary, brain, prostate, gallbladder and myeloma tumors in addition to many others. Overexpression of the c-Met oncogene has also been suggested to play a role in the pathogenesis and progression of thyroid tumors derived from follicular epithelium (Oncogene, 7:2549-2553 (1992)). HGF is a morphogen (Development, 110:1271-1284 (1990); Cell, 66:697-711 (1991)) and a potent angiogenic factor (J. Cell Biol., 119:629-641 (1992)).
Some [1,2,4]triazolo[4,3-a]-pyridine compounds, such as 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one, are selective inhibitors of the c-Met receptor, and therefore, are useful in the treatment, prevention, or amelioration of cancer. See, e.g., U.S. Pat. Nos. 8,212,041, 8,217,177, and U.S. Pat. No. 8,198,448, each of which is incorporated herein by reference in its entirety.